Percutaneous coronary intervention for coronary chronic total occlusion (CTO PCI) is offered for symptom and quality of life improvement, despite the absence of blinded randomized evidence. The aim of this study was to assess the efficacy of CTO PCI in the first randomized, placebo-controlled trial of CTO PCI. ORBITA-CTO is a multicenter, randomized, blinded trial comparing CTO PCI with a placebo procedure. Patients had angina attributable to a single-vessel CTO, without bystander coronary disease. Angina symptoms were recorded daily using the ORBITA app. After dual-injection coronary angiography, patients were randomized to either CTO PCI or placebo. Blinding was maintained using auditory isolation and deep conscious sedation. Antianginal medications were stopped at randomization and reintroduced on a patient-initiated protocol. At the 6-month follow-up, assessments were repeated. The primary efficacy outcome was the angina symptom score, an ordinal scale combining the daily symptom burden assessed by the ORBITA app, antianginal use, and over-ride events. Secondary outcomes were symptom and quality of life questionnaires and blinding fidelity. Between October 19, 2021 and October 21, 2025, 50 patients were randomly assigned to CTO PCI (n = 25) or placebo (n = 25). One patient randomized to PCI was withdrawn during the procedure because of a complication. All 50 patients were included in the primary analysis. Compared with placebo, CTO PCI resulted in an immediate and sustained improvement in the angina symptom score (OR: 4.38; 95% credible interval [CrI]: 1.57-12.69; probability of benefit [Pr{Benefit}] = 0.996), arising from a clear reduction in the number of episodes of angina (OR: 4.38; 95% CrI: 1.55-11.78; Pr[Benefit] = 0.997). This resulted in an additional 30.6 days free of angina (95% CrI: 11.1-50.7; Pr[Benefit] >0.999). Improvements were also observed with the Seattle Angina Questionnaire in angina frequency (+10.7; 95% CrI: 1.4-20.2; Pr[Benefit] = 0.988), physical limitation, quality of life, and summary score and Canadian Cardiovascular Society class. Blinding of patients, staff, and researchers was maintained. In patients with symptomatic single-vessel CTO, CTO PCI improves angina beyond placebo. (A Placebo-controlled Trial of Chronic Total Occlusion Percutaneous Coronary Intervention for the Relief of Stable Angina [ORBITA-CTO]; NCT05142215).